title: HER4 expression status correlates with improved outcome in both neoadjuvant and adjuvant Trastuzumab treated invasive breast carcinoma.
abstract: Prognostic and predictive markers utilized in invasive breast carcinoma are limited and include ER, PR, Ki67, and ERBB2 (HER2). In the case of HER2, over-expression or amplification serves as eligibility for anti-HER2 based therapy, including trastuzumab (Herceptin®, Genentech). While clinical trials have shown trastuzumab improves overall survival and time to progression, an individual's response to anti-HER2 based therapy is highly variable. This suggests that, in a "uniform" HER2 positive population, additional markers could help in predicting patient outcome to therapy. Here we utilized a recently validated high-specificity HER4 antibody (E200) and generated a standard clinical HER4 scoring algorithm (HER4 H-Score) utilizing two breast carcinoma cohorts: 1) patients receiving neoadjuvant trastuzumab (n=47) and 2) patients receiving trastuzumab for metastatic disease (n=33). Our HER4 H-Score showed significant correlation with high sensitivity RT-qPCR performed on matched patients (p=<0.0001). In addition, patients with HER2/HER4 co-over-expression status showed a significant delay in development of metastasis after neo-adjuvant trastuzumab therapy (p= 0.04) and showed a significant improvement in progression free survival after adjuvant trastuzumab therapy (p=0.03). These findings suggest HER4 IHC, used in conjunction with a standard HER2 testing algorithm, could aid in predicting clinical outcome and help identify patients likely to show improved response to trastuzumab therapy.
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist, Houston, TX.
authors.forename: Bryce P
authors.initials: BP
authors.lastname: Portier
authors.forename: Eugen C
authors.initials: EC
authors.lastname: Minca
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Christopher
authors.initials: C
authors.lastname: Lanigan
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Gruver
authors.forename: Erinn
authors.initials: E
authors.lastname: Downs-Kelly
authors.forename: G Thomas
authors.initials: GT
authors.lastname: Budd
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
mesh_terms: D000328:Adult; D000465:Algorithms; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D011379:Prognosis; D066247:Receptor, ErbB-4; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4; D000068878:Trastuzumab